Section 18.4. Synthetic Biology and Genomic Programming

18.4. Synthetic Biology and Genomic Programming

Since 1972, genetic engineering has been performed using the Cohen-Boyer recombinant techniques. These methods require DNA molecules to be extracted from cells and physically rearranged into new genetic designsa process not unlike writing a letter "ransom note" style. Done in the lab, proficiency in this work typically requires an advanced degree with practical experience, a lot of equipment and reagents, and considerable time. Even relatively mundane procedures can take experienced technicians many months of tedious work, visible only by indirect methods. Compared to other modern engineering effortsfor example, microprocessor, aircraft, or building design, today performed in computer environmentsgenetic engineering remains a crude, manual process.

The emergence of synthetic biology (SB) changes everything. Founded on automated chemistries that permit long-chain DNA to be synthesized de novo, SB is a platform of software tools used to design and test artificial DNA molecules. It is an output device for bioinformatic software, and provides scientists with a way to write DNA sequences, not just read and comprehend them. The technology greatly lowers the barriers to genomic work: anyone with access to a computer can effectively create or edit DNA with exquisite precision. Overall, by transforming DNA into a biological programming language, SB represents the biggest improvement in genetic technology since Cohen-Boyer. It advances biological design into the digital age.

More than just bringing new speed and convenience to genetics, SB brings genetic scientists an alternative to unrestricted publication or patent. It is a creative tool, one that both proprietary companies and academic researchers will use to design DNA code. However, the technology brings an opportunity to reevaluate how the resultant IP should be protected. Today patent is used almost exclusively for biotech IP, including gene sequencesbut synthetic biology makes new DNA designs into authored products like software. This type of IP is most often protected by copyright. Copyright would be inexpensive and easy to use, and would dovetail well with the application open source licenses, offering attractive IP benefits. However, without historical or legal precedent, there is no way to know how genetic copyrights would change R&D, or whether they would even be recognized as valid.

With the close similarity to software programming, synthetic biology gives OSB modeled after OSS a good chance of success. OSB could adapt the open source concepts, tools, licenses, and business models that already exist. Already, dozens of bioinformatic tools have been released under open source licenses, and software development platforms like SourceForge and Tigris could be easily modified to support DNA codewriting. Overall, for OSB based on SB to produce biological products, it would need to overcome only two main obstacles. First, it would need to attract an open developer community. Second, the genetic programs developed in the digital domain would need to be made affordably testable in real-world laboratories.

Open source synthetic biology will presumably find some support among genomic and bioinformatic scientists, many of whom currently release both data and tools openly on the Internet. However, Drew Endy, an assistant professor at MIT, is not taking any chances. He is actively seeding a new generation of biological programmers by teaching students how to build custom bacteria. Using presynthesized DNA dubbed "biobricks," or de novo code, Endy has created the biological equivalent of many electronic parts, including transistors, LEDs, and photosensors. Biobricks can be assembled in various ways to new create biological circuits, with bacterial cells the test breadboard. Biobricks form the foundation for MIT's multisite graduate student challenge, meant to encourage new synthetic designs and raise interest in synthetic techniques. The strategy is working: Endy's efforts have received wide attention in the technology press, and MIT's first conference on synthetics brought together more than 300 participants.

Endy is also a strong supporter of OSB, placing the biobricks standard registry in the public domain, a move he hopes will encourage others to use the technology and to share their own components. There is concern that unless an open ideology can be fostered, researchers might choose to patent each individual component, making biological programming a legal quagmire. Already, synthetic switches to turn genes on and off have been patented. Engineers Rob Carlson and Roger Brent, also early adopters of synthetic technologies, have warned of choosing a proprietary path and slowing innovation. In a white paper sent to DARPA, the advanced research agency of the U.S. military and an early backer of synthetic development, the pair argued that the development of a public domain "kernel" in synthetic biology could avert the negative consequences of having knowledge useful to the design of living organisms held proprietary. They maintain that biology conducted in an open manner would be, like open software, "robust and adaptive, providing for a more secure economy and country."

Great advantages could result if OSB can seed developer communities with keen interest in writing biological software. The sharing of genetic program designs openly should quickly lead to novel designs. The ability to engineer life on a computer desktop, not in a laboratory, should dissolve interdisciplinary boundaries and bring many new ideas into the biological sciences. Importantly, it allows genomic projects to aggregate and organize large numbers of developers. Online genomic development communities could blossom into virtual R&D organizations that dwarf those even of big pharma, yet be far more sustainable, open, and empowered. With inclusive membership and open data, "hobbyist" researchersincreasingly valuable contributors to astronomy, physics, and other scienceswould also enjoy the opportunity to participate meaningfully in collaborative genetic projects.

Meanwhile, the second obstacle to OSB producing a biological product, discovering inexpensive ways for genomic designs to be testable in the real world, is self-resolving. The per-base cost of long-chain DNA synthesis is dropping rapidly as commercial DNA providers compete for research customers. Today constructs that are viral size can be produced affordably. If current trends continue, human genome-size constructs will be realistic, both technologically and financially, by 2010. The economics of making commercial products with synthetics should become more attractive over time, if we can just learn how to write good code.